ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.925G>T (p.Glu309Ter)

dbSNP: rs199476360
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193048 SCV001361597 likely pathogenic Metachromatic leukodystrophy 2019-11-29 criteria provided, single submitter clinical testing Variant summary: ARSA c.925G>T (p.Glu309X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4.1e-06 in 246094 control chromosomes (gnomAD). c.925G>T has been reported in the literature in a compound heterozygous individual affected with Metachromatic Leukodystrophy (Grossi_2008). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV001193048 SCV004300065 pathogenic Metachromatic leukodystrophy 2023-07-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu309*) in the ARSA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSA are known to be pathogenic (PMID: 8962139, 10477432). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ARSA-related conditions (PMID: 18693274). This variant is also known as c.919G>T (p.E307X). ClinVar contains an entry for this variant (Variation ID: 928724). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.